Estimation of reaction free energy with multiple reaction coordinates (RCs), especially enzymatic reactions, is a very active topic in computational chemistry and biology. An effective strategy is conducting free energy simulation along a reference reaction path, preferably a minimum energy path (MEP) on the potential energy surface (PES). The free energy simulation with regard to a reference path is often involved with confining RCs to certain values corresponding to the reaction progress between two endstates. Both restraint and constraint are common choices to implement RCs confinement. Practically, it is convenient to add additional harmonic force as restraints for each RC. Although with certain advantages, there are certain difficulties when applying constraints on multiple RCs. Here we proposed a rigid structure dynamics method to sample the free energy along a reference reaction path with constraints on multiple RCs. In this method, all the key atoms to define RCs can be selected to form a rigid structure as constraints during simulations. Through a series of MD simulations with rigid structure constraints, the free energy profile can be constructed using line integral along the chosen reference pathway in free energy gradient vector field. This method is tested by several model systems to demonstrate its effectiveness.

Free energy profile along reference reaction path through rigid structure dynamics

244th National Meeting (2012)

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